One aspect of the commercial viability of an injectable drug product is long shelf life. A shelf life significantly greater than one year is typically needed. This is because drug products are often stored for long periods, for example, six months to a year or more, until needed. The expiration date of a product begins when the drug is produced, but testing and packaging for shipping often take up some time, for example, months. A shelf life of one to three years or more is very desirable for an injectable drug product. This is especially true for a drug which may be stored for a long period of time, because it is not frequently used, but that is specifically required when indicated.
Another aspect of injectable drug products is reconstitution of the formulation by the medical practitioner. The drug may be delivered in a solid form, often called “drug for injection,” which may contain other ingredients, and is reconstituted to a liquid form by the addition of solvent and other components.
A USP (United States Pharmacopeia) requirement for parenteral drug products is that the product be visibly clear before use. A vial of crystal clear liquid is desired. To meet this standard, the number of particulates in the reconstituted liquid product must be kept to a minimum. Particulates represent undissolved drug which is ineffective, and may block capillaries causing serious adverse health effects. A crystal clear drug product requires the solution to have a minimum of minute, undissolved, or non-visible drug particles.
Particulates in an injectable drug product may be caused in part by foaming during reconstitution. Foaming may be caused by the drug itself, or by surfactants other additives used to increase and hasten solubility of the drug. Foaming can prevent small particles from entering the solution to be dissolved, thereby increasing the number of particulates in the reconstituted injectable drug product.
Another aspect of parenteral drug products is the time required to reconstitute an injectable formulation. Reconstitution requires the ability to rapidly redissolve a drug composition to provide a crystal clear solution. In addition, the reconstitution should be rapid after a long storage period of the delivered drug composition, a period which can be, for example, one, two, or three years or more. Some drug compositions as delivered typically cannot achieve a shelf life greater than one year. This is because either the reconstitution time is too long after storage, or the number of particulates in the reconstituted product is too high.
Echinocandin antifungal compounds, and methods for their manufacture and use are described, for example, in PCT WO 00/52037; PCT WO 00/51564; PCT WO 00/34315; PCT WO 00/51567; and U.S. Pat. No. 5,965,525.
There is a need for echinocandin pharmaceutical drug formulations that are useful for parenteral pharmaceutical administration with rapid reconstitution, little forming, and a long shelf life.